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Review of ESF clinical trial shows increased risk of blood clots

A meta-analysis review of 57 trials and 9353 cancer patients treated with erythropoiesis-stimultating factors (ESFs) epoetin and darbepoetin culled from articles, abstracts and reports between January, 1985 and April, 2005 increased thromboembolic events.

Treatment with ESFs significantly reduced the risk for red blood cell transfusions in 36% of 6510 patients in 42 trials and improved hemoglobin levels in 22 trials and 4307 patients (RR=3.43, 95% CI=3.07 to 3.84).

Thromboembolic events were increased with treatment with epoetin or darbepoetin by 67% in 35 trials and 6769 patients (RR=1.67, 95% CI=1.35 to 2.06). How these ESFs affect overall survival is uncertain. Caution is advised when using epoetin or darbepoetin in patients that are at a high risk for thromboembolic events or in combination with thrombogenic chemotherapeutic agents.

For additional information on this research, please reference the source article:
Bohlius J, Wilson J, Seidenfeld J, Piper M, Schwarzer G, Sandercock J, Trelle S, Weingart O, Bayliss S, Djulbegovic B, Bennett CL, Langensiepen S, Hyde C, Engert A. Recombinant human erythropoietins and cancer patients: updated meta-analysis of 57 studies including 9353 patients.

Effectiveness of current ESFs not significantly different

No therapeutic difference was found between epoetin and darbepoetin in treatment of cancer patients who are undergoing chemotherapy or radiation according to a meta-analysis report by the Agency for Healthcare Research.

Both drugs reduce the need for transfusion, but no evidence that either drug improves survival in patients receiving cancer treatment. Quality of life measures favored the use of either drug, but study selection methods and reporting of results were inconsistent.

Rates of thromboembolic events were not significantly different between the two drugs. The rates varied widely, but pooled results showed approximately 7% of patients treated with either drug experienced a thromboembolic event versus 4% for untreated patients. Higher than recommended hemoglobin levels were used in some studies but evidence did not support that the increase in hemoglobin increased the risk for thromboembolic events.

For additional information on this research, please reference the source website and link to the report.
www.effectivehealthcare.ahrq.gov/reports/final.cfm
Seidenfeld J, Piper M, Bohlius J, Weingart O, Trelle S, Engert A, Skoetz N, Schwarzer G, Wilson J, Brunskill S, Hyde C, Bonnell C, Ziegler KM, Aronson N. Comparative Effectiveness of Epoetin and Darbepoetin for Managing Anemia in Patients Undergoing Cancer Treatment. Comparative Effectiveness Review No. 3. (Prepared by Blue Cross and Blue Shield Association Technology Evaluation Center Evidence-based Practice Center under Contract No. 290-02-0026.) Rockville, MD: Agency for Healthcare Research and Quality. May 2006.

Worsening anemia in advanced prostate cancer predicts shorter survival

Researchers studying hormonal treatment for metastatic prostate cancer found that anemia worsening over a 3 month period after androgen deprivation therapy was associated with a shorter survival and shorter progression-free survival after adjustment for disease status and other baseline covariates.

The median pre-treatment hemoglobin was 13.7 g/dL. After 3 months the mean change in hemoglobin decreased 0.54 g/dL, but increased by 0.99 g/dL in patients with a baseline hemoglobin < 12 g/dL , and decreased 1.04 g/dl in those with a baseline >12 g/dL. A decline in hemoglobin after 3 months of treatment was independently associated with a shorter overall survival.

Surprisingly, the researchers found that black patients had a worse overall outcome than non-blacks if their baseline hemoglobin was below 11.7 g/dL. Blacks had better outcomes than non-blacks if their baseline hemoglobin was above 11.7 g/dL.

While race alone was not a strong predictor of death or disease progression, the effect of baseline hemoglobin on survival varied significantly by race. Further study is needed to understand the biology of this affect and to determine if reversing the anemia can improve survival in patients with advanced prostate cancer.

For additional information on this research, please reference to source presentation:
(1197) Prognostic value of hemoglobin change after initiation of androgen deprivations therapy for newly diagnosed metastatic prostate cancer: a multivariate analysis of SWOG 8894.
Beer T, Goldman B, Tangen C, Bland L, Hussain M, DeLoughery T, Crawford D.
AUA Annual Meeting Abstract No. 1197. May 2006. Podium: POD18. Prostate Cancer: Advanced (II).

Darbepoetin improves hemoglobin levels, fatigue in myelodysplastic syndromes

Darbepoetin administered every 3 weeks to patients who had never received an erythropoiesis-stimulating agent, dramatically increased hemoglobin levels and improved patient-reported fatigues in patients with low-risk myelodysplastic syndromes (MDS).

Patients with myelodysplastic syndromes, or "pre-leukemia", often develop anemia resulting in increased transfusions and fatigue. Use of epoetin alfa to treat low-risk MDS patients results in an average response rate of 30%. Pilot studies suggest using 150-300mcg/week of darbepoetin alfa can also raise hemoglobin levels.

In a phase II trial using 500 mcg of darbepoetin every 3 weeks in erythropoiesis-stimulating-agent naïve patients, the mean increase in hemoglobin of 1.2 g/dL. Of the 129 patients analyzed after 27 weeks, 83% reported an adverse event and none reported a serious treatment-related adverse events or a thrombolic event.

For additional information on this research, please reference the source poster presentation:
R. Paquette, J. Gabrilove, R. Lyons, C. Mushtaq, M. Sekeres, H. Lam, L. Dreiling Darbepoetin alfa for treating anemia in low-risk myelodysplastic syndrome patients: Interim results after 27/28 weeks. Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings Part I. Vol 24, No. 18S (June 20 Supplement), 2006: Abstract 6564.
2006 ASCO Annual Meeting

Anemia unchanged with androgen therapy and erythropoietin in renal failure

Patients with renal failure were often treated with androgen supplementation prior to the introduction of recombinant human erythropoietin. Since hypogonadism is common in renal dialysis patients, it was thought that the low androgen levels might contribute to anemia of renal failure.

This phase IV study evaluated 40 hypogonadal men age 18 years and older with hemo-dialysis dependent end-stage renal disease. All were treated with recombinant human erythropoietin in a range from 182 U/kg/wk to 246 U/kg/wk. One group received, in addition, topical 1% testosterone gel; the other, a placebo gel. The end point was a change in the end point dose of erythropoietin.

Results of the study indicated that administration of 100 mcg of testosterone 1% gel failed to impact the recombinant human erythropoietin requirement or clinical parameters.

Validity concerns addressed the small population, patient compliance and testosterone dosage.

For additional information on this research, please reference the source article:
Brockenbrough AT, Dittrich MO, Page ST, Smith T, Stivelman JC, Bremner WJ.
Transdermal androgen therapy to augment EPO in the treatment of anemia of chronic renal disease. Am J Kidney Dis. 2006 Feb;47(2):251-62.

Predictive model for anemia development in cancer patients developed

A risk model was developed and validated for cancer patients undergoing chemotherapy identifying patients who would be most likely to become anemic.

Five variables were identified as statistically significant for anemia prediction. 1). Lower initial hemoglobin (<13.4 g/dL in males; <12.9 g/dL in females); 2). Cancer type (gynecologic cancer or lung cancer versus gastrointestinal/colorectal cancer); 3). Cancer at any other site versus GI/colorectal cancer; 4). Treatment with platinum containing chemotherapy, and 5). Female gender.

Researchers stated that this model can be used to predict the risk for anemia in non-anemic patients prior to initiating chemotherapy and can improve quality of life by enabling health providers to manage anemia early.

For additional information on this research, please reference the source article:
Barrett-Lee PJ, Ludwig H, Birgegard G, Bokemeyer C, Gascon P, Kosmidis PA, Krzakowski M, Nortier JW, Kongable G, Schneider M, Schrijvers D, Van Belle SJ; European Cancer Anaemia Survey Advisory Board and Participating Centers. Independent risk factors for anemia in cancer patients receiving chemotherapy: results from the European Cancer Anaemia Survey. Oncology. 2006;70(1):34-48. Epub 2006 Feb 21.

New guidelines recommend erythropoietin as standard care of practice

The Kidney Disease Outcomes Quality Initiative (KDOQI) of the National Kidney Foundation updated and expanded the guidelines in April 2005 including new changes in the management of anemia in patients with chronic renal disease.

The changes come about as anemia is recognized as a "uremia-specific" risk for cardiovascular disease because of its impact on left ventricular hypertrophy and coronary artery disease.

The guideline update states that anemia is readily amenable to treatment and use of erythropoietin feasible and a standard care of practice.

For additional information on these guidelines, please reference the source article: K/DOQI clinical practice guidelines for cardiovascular disease in dialysis patients. American Journal of Kidney Diseases, Volume 45, Issue (Supplement 3), Pages 16-153 (April 2005)